Evaluation of the safety and efficacy of pathotropic nanoparticles bearing a dominant negative cyclin G1 construct for chemoresistant osteosarcoma and other sarcomas: Phase I, II, and III studies

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 10513-10513 ◽  
Author(s):  
S. P. Chawla ◽  
V. S. Chua ◽  
L. Fernandez ◽  
D. Quon ◽  
A. Saralou ◽  
...  
Keyword(s):  
Overall Survival ◽  
Phase I ◽  
Phase Ii ◽  
Dose Response ◽  
Stable Disease ◽  
Phase Ii Study ◽  
Progression Free Survival ◽  
Response Relationship ◽  
Dose Response Relationship ◽  
Free Survival

10513 Background: (1) To evaluate the safety/anti-tumor potential of intravenous (i.v.) Rexin-G in chemotherapy-resistant sarcoma (Phase I/II), and (2) to confirm the efficacy/safety of i.v. Rexin-G in chemotherapy-resistant osteosarcoma (Phase II). Methods: Twenty patients in the Phase I/II study and 22 patients in the Phase II study received 1–2 × 10e11 cfu Rexin-G i.v., 2–3 times a week for 4 weeks. Treatment was continued if the patient had < Grade 1 toxicity. Results: Treatment-related adverse events included chills (n=1), presyncope (n=1), photophobia (n=1) of Grade 1 severity, and fatigue (n=4) of Grade 1–2 severity. In the Phase I/II sarcoma study, 3/6 patients had stable disease at Dose Level 0, median progression free survival (PFS) was 5 weeks, and overall survival (OS) was 14 weeks, while 10/14 patients had stable disease at Dose Level I-II, median PFS was 16 weeks and median OS was 34 weeks. Cox regression analysis showed a dose-response relationship between PFS/OS and Rexin-G dosage (p = 0.02 and 0.005, respectively). The Table below shows the results for evaluable patients (n=17) in the Phase II study for osteosarcoma. Kaplan-Meier analysis shows a dose-response relationship between overall survival and Rexin-G dosage in the combined Phase I/II sarcoma and Phase II osteosarcoma studies (p = 0.02; n=42). Two patients achieved surgical remissions which are sustained for >26 weeks. Conclusions: These studies suggest that (i) intravenous Rexin-G is safe and well-tolerated, and (ii) Rexin-G controls tumor growth and prolongs progression-free survival and overall survival in a dose-dependent manner in chemotherapy-resistant osteosarcoma and sarcoma. [Table: see text] [Table: see text]

scholarly journals A Phase II Study of Glembatumumab Vedotin for Metastatic Uveal Melanoma

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2270
Author(s):  
Merve Hasanov ◽  
Matthew J. Rioth ◽  
Kari Kendra ◽  
Leonel Hernandez-Aya ◽  
Richard W. Joseph ◽  
...  
Keyword(s):  
Overall Survival ◽  
Uveal Melanoma ◽  
Phase Ii ◽  
Stable Disease ◽  
Objective Response Rate ◽  
Response Rate ◽  
Phase Ii Study ◽  
Objective Response ◽  
Progression Free Survival ◽  
Free Survival

Glembatumumab vedotin (CDX-011, GV) is a fully human Immunoglobulin G2 monoclonal antibody directed against glycoprotein NMB coupled via a peptide linker to monomethyl auristatin E (MMAE), a potent cytotoxic microtubule inhibitor. This phase II study evaluated the overall response rate and safety of GV, glycoprotein NMB (GPNMB) expression, and survival in patients with metastatic uveal melanoma. Eligible patients with metastatic uveal melanoma who had not previously been treated with chemotherapy received GV 1.9 mg/kg every three weeks. The primary endpoint was the objective response rate (ORR). Secondary endpoints included GPNMB expression, progression-free survival (PFS), overall survival (OS), and toxicity analysis. GPNMB expression was assessed pre- and post-treatment via immunohistochemistry for patients with available tumor tissue. Out of 35 patients who received treatment, two patients had confirmed partial responses (PRs; 6%), and 18 patients had a stable disease (SD; 51%) as the best objective response. 38% of the patients had stable disease >100 days. The grade 3 or 4 toxicities that occurred in two or more patients were neutropenia, rash, hyponatremia, and vomiting. The median progression-free survival was 3.1 months (95% CI: 1.5–5.6), and the median overall survival was 11.9 months (95% CI 9.0–16.9) in the evaluable study population. GV is well-tolerated in metastatic uveal melanoma. The disease control rate was 57% despite a low objective response rate. Exploratory immune correlation studies are underway to provide insight into target saturation, combination strategies, and antigen release.

Phase II study of dexamethasone, ascorbic acid, thalidomide and arsenic trioxide (DATA) in high risk previously untreated (PU) and relapsed/refractory (RR) multiple myeloma (MM)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 17535-17535 ◽  
Author(s):  
R. C. Baz ◽  
M. Kelly ◽  
J. Reed ◽  
M. Karam ◽  
B. Faiman ◽  
...  
Keyword(s):  
Ascorbic Acid ◽  
High Risk ◽  
Arsenic Trioxide ◽  
Phase Ii ◽  
Stable Disease ◽  
Plasma Cells ◽  
Phase Ii Study ◽  
Progression Free Survival ◽  
Free Survival ◽  
Median Progression Free Survival

17535 Background: The combination of Thalidomide (T) and Dexamethasone (D) is often used first line in patients with MM. Arsenic trioxide (ATO) is active and well tolerated in patients with RR MM. ATO, D and T have non-overlapping toxicity. We therefore initiated a phase II study to assess the efficacy and toxicity of this combination in patients with high risk PU MM (serum B2 microglobulin>5.5, chromosome 13 or 14 abnormalities by FISH or the presence of peripheral plasma cells) and RR MM. Methods: On week 1, ATO was given at a dose of 0.25mg/kg IV on days 1–5. On weeks 2–12, ATO was given at the same dose twice weekly. On weeks 13–16, the patients did not receive treatment. Ascorbic acid 1000mg IV was given after each ATO infusion. D was given at a dose of 20mg orally on days 1–4 of a 28 days cycle, and T was started at a dose of 50mg daily and increased as tolerated to a dose of 100mg daily. A similar 16 weeks consolidation course was given. Maintenance included ATO 0.25mg/kg on days 1,8,15 and 22 every 12 weeks in addition to the above schedule for D, T and Ascorbic acid. Results: Sixteen patients were enrolled (3 with PU and 13 RR), 13 are evaluable for response. The median age was 57 years and 62% were males. The median number of prior chemotherapy regimen is 2 (range 0–6), 7 patients had received a prior T containing regimen, and 2 patients had received an ATO-containing regimen. Seven, seven and two patients had SWOG stages 2, 3 and 4 respectively. The mean serum B2 microglobulin was 7.1-mg/dL (s.d. 4.4). After a median follow up of 9.5 months (range 1–12), 9 patients progressed and 5 died. The median progression free survival was 9.4 months. The median progression free survival for responder has not been reached. Four patients had a PR (31%), 8 had stable disease (62%), and 1 had progressive disease. No patient had a QT>500 or a cardiac arrhythmia. Grade 3 leukopenia, anemia, neuropathy and renal failure occurred in 3, 2, 1 and 1 patients respectively. Three patients had a venous thromboembolic event (2 DVT and 1 PE). Conclusions: The addition of T to the combination of ATO, Ascorbic acid and D is safe, well tolerated and results in 30% PR and 61% stable disease in patients with poor risk MM. [Table: see text]

Dose-Intense Chemotherapy Every 2 Weeks With Dose-Intense Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone May Improve Survival in Intermediate- and High-Grade Lymphoma: A Phase II Study of the Southwest Oncology Group (SWOG 9349)

2003 ◽  
Vol 21 (13) ◽  
pp. 2466-2473 ◽  
Author(s):  
Douglas W. Blayney ◽  
Michael L. LeBlanc ◽  
Thomas Grogan ◽  
Ellen R. Gaynor ◽  
Robert A. Chapman ◽  
...  
Keyword(s):  
Overall Survival ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Standard Dose ◽  
Progression Free Survival ◽  
High Grade ◽  
Oncology Group ◽  
Group Setting ◽  
Free Survival ◽  
Southwest Oncology Group

Purpose: To test the hypothesis that therapy of intermediate- and high-grade (excluding Burkitt lymphoblastic) lymphoma with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) could be safely dose-intensified with routine filgrastim support. Patients and Methods: Eligible patients were those who were previously untreated and who had either bulky stage II, or stage III or IV lymphoma with working formulation histology D, E, F, G, H, or J; performance status ≤ 2; and acceptable end organ function. No upper age limit was specified. Therapy was dose-intensified CHOP (CHOP-DI) with filgrastim support. Each course was repeated every 14 days for six planned courses. Results: Eighty-eight eligible patients were treated with CHOP-DI and had a median follow-up of 5.1 years on this phase II study, designated Southwest Oncology Group (SWOG) 9349. The progression-free survival was 51% at 2 years and 41% at 5 years. The overall survival was 60% at 5 years. Three fatal treatment-related events occurred. One patient with myelodysplastic syndrome was reported. Conclusion: Treatment with CHOP-DI can be safely administered in the cooperative group setting and results in improved survival. Estimated overall survival at 5 years was 14% better than that of patients treated with standard-dose CHOP in an earlier SWOG study, although progression-free survival of 60% at 2 years—the prespecified end point—was not achieved. CHOP-DI, given every 2 weeks at escalated doses, is a strategy that should be tested in a future randomized clinical trial in lymphoma.

scholarly journals Phase II Study of Sorafenib in Combination With Docetaxel and Cisplatin in the Treatment of Metastatic or Advanced Gastric and Gastroesophageal Junction Adenocarcinoma: ECOG 5203

2010 ◽  
Vol 28 (18) ◽  
pp. 2947-2951 ◽  
Author(s):  
Weijing Sun ◽  
Mark Powell ◽  
Peter J. O'Dwyer ◽  
Paul Catalano ◽  
Rafat H. Ansari ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Phase Ii ◽  
Group Performance ◽  
Phase Ii Study ◽  
Performance Status ◽  
Gastroesophageal Junction ◽  
Eastern Cooperative Oncology Group ◽  
Progression Free Survival ◽  
Free Survival

Purpose The combination of sorafenib with chemotherapy is well-tolerated and is associated with encouraging response rates in several malignances. Both docetaxel and cisplatin are active in gastric cancer. A phase II study was conducted to determine the efficacy and toxicity of combined sorafenib, docetaxel, and cisplatin in patients with metastatic or advanced adenocarcinoma of stomach or gastroesophageal junction (GEJ). Patients and Methods Forty-four chemotherapy-naïve patients with Eastern Cooperative Oncology Group performance status 0 or 1, of whom 80% had metastatic disease and two thirds had poorly differentiated gastric or GEJ adenocarcinoma, were enrolled. The treatment regimen was sorafenib 400 mg orally twice a day for 21 days, docetaxel 75 mg/m2 intravenously on day 1, and cisplatin 75 mg/m2 intravenously on day 1, repeated every 21 days. The primary end point was response rate to the combination. Toxicity, overall survival, and progression-free survival were assessed as secondary end points. Results Eighteen of the 44 eligible and treated patients showed partial responses (41%; 90% CI, 28% to 54%). The median progression-free survival was 5.8 months (90% CI, 5.4 to 7.4 months). The median overall survival was 13.6 months (90% CI, 8.6 to 16.1 month). The major toxicity of this regimen was neutropenia, which reached grade 3 to 4 in 64% of patients. One patient experienced hemorrhage at the tumor site. Conclusion The combination of sorafenib, docetaxel, and cisplatin has an encouraging efficacy profile with tolerable toxicity. Additional studies of sorafenib with chemotherapy are warranted in gastric cancer.

Randomized Phase II Study Comparing Gemcitabine Plus Dacarbazine Versus Dacarbazine Alone in Patients With Previously Treated Soft Tissue Sarcoma: A Spanish Group for Research on Sarcomas Study

2011 ◽  
Vol 29 (18) ◽  
pp. 2528-2533 ◽  
Author(s):  
Xavier García-del-Muro ◽  
Antonio López-Pousa ◽  
Joan Maurel ◽  
Javier Martín ◽  
Javier Martínez-Trufero ◽  
...  
Keyword(s):  
Overall Survival ◽  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Progression Free Survival ◽  
Fixed Dose ◽  
Disease Rate ◽  
Free Survival ◽  
Previously Treated

Purpose To assess the activity and toxicity of the combination of gemcitabine plus dacarbazine (DTIC) in patients with advanced soft tissue sarcoma (STS) in a randomized, multicenter, phase II study using DTIC alone as a control arm. Patients and Methods Patients with previously treated advanced STS were randomly assigned to receive either fixed-dose rate gemcitabine (10 mg/m2/min) at 1,800 mg/m2 followed by DTIC at 500 mg/m2 every 2 weeks, or DTIC alone at 1,200 mg/m2 every 3 weeks. The primary end point of the study was progression-free rate (PFR) at 3 months. Results From November 2005 to September 2008, 113 patients were included. PFR at 3 months was 56% for gemcitabine plus DTIC versus 37% for DTIC alone (P = .001). Median progression-free survival was 4.2 months versus 2 months (hazard ratio [HR], 0.58; 95% CI, 0.39 to 0.86; P = .005), and median overall survival was 16.8 months versus 8.2 months (HR, 0.56; 95% CI, 0.36 to 0.90; P = .014); both favored the arm of gemcitabine plus DTIC. Gemcitabine plus DTIC was also associated with a higher objective response or higher stable disease rate than was DTIC alone (49% v 25%; P = .009). Severe toxicities were uncommon, and treatment discontinuation for toxicity was rare. Granulocytopenia was the more common serious adverse event, but febrile neutropenia was uncommon. Asthenia, emesis, and stomatitis were the most frequent nonhematologic effects. Conclusion The combination of gemcitabine and DTIC is active and well tolerated in patients with STS, providing in this phase II randomized trial superior progression-free survival and overall survival than DTIC alone. This regimen constitutes a valuable therapeutic alternative for these patients.

scholarly journals Phase II Trial of Angiotensin-(1-7) for the Treatment of Patients with Metastatic Sarcoma

Sarcoma ◽  
2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Paul D. Savage ◽  
James Lovato ◽  
K. Bridget Brosnihan ◽  
Antonius A. Miller ◽  
W. Jeffrey Petty
Keyword(s):  
Phase I ◽  
Phase Ii ◽  
Phase I Study ◽  
Phase Ii Study ◽  
Progression Free Survival ◽  
Epithelioid Hemangioendothelioma ◽  
Free Survival ◽  
Disease Stabilization ◽  
Prospective Phase ◽  
Metastatic Sarcoma

Background. Angiotensin-(1-7) [Ang-(1-7)] is an endogenous antiangiogenic hormone with anticancer activity. In a phase I study of Ang-(1-7), two of three patients with metastatic sarcoma experienced disease stabilization. This phase II study examined clinical and biomarker outcomes for patients with metastatic sarcoma. Methods. Ang-(1-7) was administered by subcutaneous injection at a dose of 20 mg daily. If excessive toxicities occurred in the first cohort, a dose deescalation cohort was allowed. Blood samples were obtained to measure changes in biomarkers. Results. Treatment was well-tolerated and the dose deescalation cohort was not required. Plasma PlGF concentrations following treatment were not statistically significantly changed. A significant increase in plasma Ang-(1-7) was observed at 4 hours after injection. The median progression-free survival was 2.7 months (95% CI; 1.4 to 4.1 months), and the median overall survival was 10.2 months (95% CI; 5.3 to 18.3 months). Two patients with vascular sarcomas demonstrated prolonged disease stabilization of 10 months (hemangiopericytoma) and 19 months (epithelioid hemangioendothelioma). Conclusions. Ang-(1-7) at a dose of 20 mg daily was well-tolerated. This prospective phase II study failed to confirm the PlGF biomarker effect identified in the prior phase I study. Prolonged disease stabilization in hemangiopericytoma and epithelioid hemangioendothelioma may warrant further investigation.

Multicenter phase II study evaluating docetaxel (D) and cisplatin (C) as an induction regimen prior to surgery or radiochemotherapy (RCT) with D, followed by adjuvant D in chemonaive patients with NSCLC: TAX-AT1–203

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7702-7702
Author(s):  
R. Greil ◽  
W. Pfeifer ◽  
N. Vetter ◽  
J. Eckmayr ◽  
O. Burghuber ◽  
...  
Keyword(s):  
Overall Survival ◽  
Induction Chemotherapy ◽  
Phase Ii ◽  
Response Rate ◽  
Phase Ii Study ◽  
Progression Free Survival ◽  
Free Survival ◽  
Secondary Endpoints ◽  
Grade 3 ◽  
D 20

7702 Background: This phase II study evaluated operable and unresectable patients (pts) treated with induction chemotherapy with DC to assess the response rate and conversion to resectability. Furthermore, the feasibility and efficacy of radiosensitizing with D was tested in unresectable pts undergoing RCT. The feasibility of adjuvant D was investigated in all patients. Study Design: Pts with stages II, IIIA and IIIB NSCLC were treated with 3 cycles of 3-wkly neoadjuvant D (75 mg/m2 d 1) and C (40 mg/m2 d1, 2). Within 4 wk after induction, pts were either resected or treated with RCT (2 Gy × 5d for 6 wk) and D 20 mg/m2 wkly × 6 cycles. Within 4–8 wk after definitive RCT or surgery, 3 cycles of adjuvant D 75 mg/m2 q3wk were initiated. Adjuvant RT was allowed in non-R0 resected cases. The primary endpoint was response rate to induction; secondary endpoints included resectability after induction, progression-free survival, overall survival, and safety. Results: 77 pts were included: age 60 yr [46–76 yr], males 78%, stages (II/IIIA/IIIB: 8%/39%/52%), primary resectability n=22 (29%), primary unresectability n=55 (71%). 59 patients were evaluable after induction chemotherapy, of whom 66% achieved a PR, 23% had stable disease, and 10% progressed. The PR rate was 73% in initially resectable and 63% in initially unresectable pts. 67 pts were evaluable for resectability. 28/39 (72%) of PR patients were resectable. As a result of induction therapy, 19 pts (25%) became resectable, 18 (24%) remained resectable, 27 (35%) remained unresectable, and 3 (4%) became unresectable. Treatment had to be stopped in 11 pts during induction. Three pts, primarily unresectable (4%) died of toxicity. 53% of patients had a grade 3 or 4 toxicity. In evaluable pts, the median PFS was 350 [80–1495] days vs 192 [21–989] days for resectable and unresectable pts after induction, respectively, and overall survival was 491 vs 303 days. Conclusions: DC induction chemotherapy resulted in a promising PR rate and rate of secondary resectability. The toxicity is substantial. Results of efficacy and toxicity of radiosensitizing and adjuvant D are pending. No significant financial relationships to disclose.

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